Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

// Teresa Bernadette Steinbichler 1 , Abdelmoez Alshaimaa 2 , Metzler Veronika Maria 1 , Dejaco Daniel 1 , Riechelmann Herbert 1 , Dudas Jozsef 1 and Skvortsova Ira-Ida 2 1 Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria 2 Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, Innsbruck, Austria Correspondence to: Teresa Bernadette Steinbichler, email: teresa.steinbichler@tirol-kliniken.at Keywords: epithelial to mesenchymal transition; chemoresistance; clonogenic assays; ERCC1; survivin Received: April 25, 2017      Accepted: December 04, 2017      Published: December 14, 2017 ABSTRACT Objective: Epithelial-mesenchymal crosstalk (EMC) contributes to tumor progression, chemoresistance and acquisition of a mesenchymal phenotype (EMT) of cancer cells. This study aims to investigate the effects of EMC on radioresistance in head and neck squamous cell carcinoma (HNSCC) cells. Methods: In tumor cell lines, the response of HNSCC cells, stimulated with EMC conditioned medium (CM), to irradiation was evaluated with viability and clonogenic assays. Dose modifying factors (DMF) were calculated from the results of clonogenic assays. Potential pathways involved in radioresistance were analyzed with quantitative Real-Time PCR and western blot. Results: CM significantly reduced the doubling time of SCC-25 cells (from 32.8 hours to 16.8 hours, p=0.0001) and Detroit 562 cells (from 88.5 hours to 29.6 hours, p=0.014). Further it increased clonogenic survival after irradiation. The DMF of CM was 2.04 ± 0.43 (mean ± standard deviation) for SCC-25 cells (p=0.015) and 2.14 ± 0.34 for Detroit 562 cells (p=0.008). Treatment with CM more than tripled the ERCC1 and survivin gene expression in SCC-25 cells. Conclusion: EMC induced pathways involved in cell survival and DNA repair and led to increased radioresistance in HNSCC cells.